In order to assign the genes for chorionic gonadotropin (hCG) to specific chromosomes, human choriocarcinoma cells have been fused with mouse fibroblasts producing a series of human:mouse somatic cell hybrids. These hybrid strains have been evaluated for hCG production and analyzed for human chromosome content. No single chromosome was uniformly present in hCG positive hybrids and absent in hCG negative hybrids. However, the combination of human chromosomes 10 and 18 seemed necessary for synthesis of hCG. Since hCG is a glycoprotein composed of two dissimilar subunits, it seemed possible that the genes for each subunit were on different chromosomes or that genes on one chromosome had a regulatory or important metabolic effect on the structure genes located on the other chromosome. For that reason, nucleic acid hybridization studies have been initiated to examine the relationship between the presence of the structural genes for the alpha and beta subunits and hormone synthesis in the somatic cell hybrids. Specific cDNA probes for the alpha subunit and beta subunit of hCG are being used for nucleic acid hybridization studies with DNA extracted from a variety of mouse:human hybrid cells. The DNA isolated from both hCG positive and negative cells has been digested with restriction endonucleases, subjected to agarose gel electrophoresis, and transferred to nitrocellulose filters. The specific 32P-labeled cDNA for the alpha or beta subunit in RNA will be incubated with the DNA from the hybrid cells and analyzed by radioautography. These studies should permit assignment of the structural genes for the alpha and beta subunits to specific human chromosomes and should also provide a system for evaluating the genetic, cellular, and extracellular factors controlling hCG synthesis in these cells.